Suberoylanilide Hydroxamic Acid Attenuates Autoimmune Arthritis by Suppressing Th17 Cells through NR1D1 Inhibition
Rheumatoid arthritis (RA) is a type of systemic autoimmune arthritis that causes joint inflammation and destruction. One of the pathological mechanisms of RA is known to involve histone acetylation. Although the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) can attenuat...
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| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/5648987 |
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| author | Da Som Kim Hong-Ki Min Eun Kyung Kim Seung Cheon Yang Hyun Sik Na Seon-Yeong Lee Jeong-Won Choi Kyung-Ah Jung Seung-Ki Kwok Sung-Hwan Park Mi-La Cho |
| author_facet | Da Som Kim Hong-Ki Min Eun Kyung Kim Seung Cheon Yang Hyun Sik Na Seon-Yeong Lee Jeong-Won Choi Kyung-Ah Jung Seung-Ki Kwok Sung-Hwan Park Mi-La Cho |
| author_sort | Da Som Kim |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is a type of systemic autoimmune arthritis that causes joint inflammation and destruction. One of the pathological mechanisms of RA is known to involve histone acetylation. Although the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) can attenuate arthritis in animal models of RA, the mechanism underlying this effect is poorly understood. This study was performed to examine whether SAHA has therapeutic potential in an animal model of RA and to investigate its mechanism of action. Collagen-induced arthritis (CIA) mice were orally administered SAHA daily for 8 weeks and examined for their arthritis score and incidence of arthritis. CD4+ T cell regulation following SAHA treatment was confirmed in splenocytes cultured under type 17 helper T (Th17) cell differentiation conditions. Clinical scores and the incidence of CIA were lower in mice in the SAHA treatment group compared to the controls. In addition, SAHA inhibited Th17 cell differentiation, as well as decreased expression of the Th17 cell-related transcription factors pSTAT3 Y705 and pSTAT3 S727. In vitro experiments showed that SAHA maintained regulatory T (Treg) cells but specifically reduced Th17 cells. The same results were obtained when mouse splenocytes were cultured under Treg cell differentiation conditions and then converted to Th17 cell differentiation conditions. In conclusion, SAHA was confirmed to specifically inhibit Th17 cell differentiation through nuclear receptor subfamily 1 group D member 1 (NR1D1), a factor associated with Th17 differentiation. The results of the present study suggested that SAHA can attenuate CIA development by inhibition of the Th17 population and maintenance of the Treg population through NR1D1 inhibition. Therefore, SAHA is a potential therapeutic candidate for RA. |
| format | Article |
| id | doaj-art-e2ce1fafbe5947839cbcf0a75e5bf5a5 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-e2ce1fafbe5947839cbcf0a75e5bf5a52025-02-03T01:24:22ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/56489875648987Suberoylanilide Hydroxamic Acid Attenuates Autoimmune Arthritis by Suppressing Th17 Cells through NR1D1 InhibitionDa Som Kim0Hong-Ki Min1Eun Kyung Kim2Seung Cheon Yang3Hyun Sik Na4Seon-Yeong Lee5Jeong-Won Choi6Kyung-Ah Jung7Seung-Ki Kwok8Sung-Hwan Park9Mi-La Cho10The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDivision of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaImpact Biotech, Seoul, Republic of KoreaDivision of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDivision of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaRheumatoid arthritis (RA) is a type of systemic autoimmune arthritis that causes joint inflammation and destruction. One of the pathological mechanisms of RA is known to involve histone acetylation. Although the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) can attenuate arthritis in animal models of RA, the mechanism underlying this effect is poorly understood. This study was performed to examine whether SAHA has therapeutic potential in an animal model of RA and to investigate its mechanism of action. Collagen-induced arthritis (CIA) mice were orally administered SAHA daily for 8 weeks and examined for their arthritis score and incidence of arthritis. CD4+ T cell regulation following SAHA treatment was confirmed in splenocytes cultured under type 17 helper T (Th17) cell differentiation conditions. Clinical scores and the incidence of CIA were lower in mice in the SAHA treatment group compared to the controls. In addition, SAHA inhibited Th17 cell differentiation, as well as decreased expression of the Th17 cell-related transcription factors pSTAT3 Y705 and pSTAT3 S727. In vitro experiments showed that SAHA maintained regulatory T (Treg) cells but specifically reduced Th17 cells. The same results were obtained when mouse splenocytes were cultured under Treg cell differentiation conditions and then converted to Th17 cell differentiation conditions. In conclusion, SAHA was confirmed to specifically inhibit Th17 cell differentiation through nuclear receptor subfamily 1 group D member 1 (NR1D1), a factor associated with Th17 differentiation. The results of the present study suggested that SAHA can attenuate CIA development by inhibition of the Th17 population and maintenance of the Treg population through NR1D1 inhibition. Therefore, SAHA is a potential therapeutic candidate for RA.http://dx.doi.org/10.1155/2019/5648987 |
| spellingShingle | Da Som Kim Hong-Ki Min Eun Kyung Kim Seung Cheon Yang Hyun Sik Na Seon-Yeong Lee Jeong-Won Choi Kyung-Ah Jung Seung-Ki Kwok Sung-Hwan Park Mi-La Cho Suberoylanilide Hydroxamic Acid Attenuates Autoimmune Arthritis by Suppressing Th17 Cells through NR1D1 Inhibition Mediators of Inflammation |
| title | Suberoylanilide Hydroxamic Acid Attenuates Autoimmune Arthritis by Suppressing Th17 Cells through NR1D1 Inhibition |
| title_full | Suberoylanilide Hydroxamic Acid Attenuates Autoimmune Arthritis by Suppressing Th17 Cells through NR1D1 Inhibition |
| title_fullStr | Suberoylanilide Hydroxamic Acid Attenuates Autoimmune Arthritis by Suppressing Th17 Cells through NR1D1 Inhibition |
| title_full_unstemmed | Suberoylanilide Hydroxamic Acid Attenuates Autoimmune Arthritis by Suppressing Th17 Cells through NR1D1 Inhibition |
| title_short | Suberoylanilide Hydroxamic Acid Attenuates Autoimmune Arthritis by Suppressing Th17 Cells through NR1D1 Inhibition |
| title_sort | suberoylanilide hydroxamic acid attenuates autoimmune arthritis by suppressing th17 cells through nr1d1 inhibition |
| url | http://dx.doi.org/10.1155/2019/5648987 |
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